IL-1 receptor 2 (IL-1R2) and its role in immune regulation

The cytokine IL-1 is critical to the pathogenesis of a variety of human conditions and diseases. Unlike most other cytokines, IL-1 is counterbalanced by two endogenous inhibitors. The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra. In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1. While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling. IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP). Additionally, IL-1R2 exists in both a membrane bound and soluble form (sIL-1R2) that has biological properties similar to both a decoy receptor and a binding protein. Thus far, IL-1R2 has been implicated in arthritis, endometriosis, organ transplantation, sepsis/sickness behavior, diabetes, atherosclerosis, autoimmune inner ear disease (AIED), Alzheimer's disease and ulcerative colitis. In this review, we will detail the functional properties of IL-1R2 and examine its role in human disease.